a study of gc012f (azd0120), a car t therapy targeting cd19 and bcma in subjects with relapsed/refractory multiple myeloma

Conditions: Relapsed/ Refractory Multiple Myeloma

Summary: this trial is a phase 1b/2, open-label, multicenter study of gc012f (azd0120), a cd19/bcma dual cart-cell therapy, in adult subjects with relapsed/refractory multiple myeloma.

for phase ib it aims to evaluate the safety, tolerability, pharmacokinetic characteristics, pharmacodynamic effect, immunogenicity in subjects with relapsed/ refractory multiple myeloma, and determine the recommended phase 2 dose of gc012f (azd0120). for phase 2, it aims to evaluate the efficacy, to further characterize the safety of gc012f (azd0120), pharmacodynamic effect, and immunogenicity, changes from baseline for subject-reported health-related quality of life, overall health status in subjects with relapsed/ refractory multiple myeloma.

Eligibility criteria:
inclusion criteria: * males and females ≥18 years of age at the time of consent * written informed consent in accordance with federal, local, and institutional guidelines * have an ecog performance status of 0 or 1 * documented diagnosis of mm per imwg diagnostic criteria * received at least three prior mm treatment lines of therapy * have received as part of their previous therapy a pi and imid and an anticd38 antibody. * have documented evidence of progressive disease by the imwg criteria. * subjects must have measurable disease at screening, as defined by any of the following: serum monoclonal paraprotein (m-protein) ≥1.0g/dl (10 g/l); urine m-protein ≥200 mg/24 h; serum flc assay: involved flc level is ≥10 mg/dl (100 mg/l) and serum kappa lambda flc ratio is abnormal. * adequate bone marrow and organ function assessment at screening according to the hematological, hepatic, and renal parameters listed in the csp exclusion criteria : * diagnosed or treated for invasive malignancy other than multiple myeloma, except: malignancy treated with curative intent and with no known active disease present for ≥2 years before enrollment; or * adequately treated non-melanoma skin cancer without evidence of disease. * the following cardiac conditions: * new york heart association (nyha) stage iii or iv congestive heart failure * myocardial infarction or coronary artery bypass graft (cabg) ≤6 months prior to enrollment * history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration * history of severe non-ischemic cardiomyopathy * received either of the following: * an allogenic stem cell transplant within 6 months before apheresis. subjects who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (gvhd). * an autologous stem cell transplant ≤12 weeks before apheresis * known active, or prior history of central nervous system (cns) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. * plasma cell leukemia at the time of screening (\>2.0×109 /l plasma cells by standard differential), waldenström's macroglobulinemia, poems syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary al amyloidosis.

Keywords: multiple myeloma, bcma, car